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  • The EMBO Journal (2003) 22, 2634 - 2644
  • doi:10.1093/emboj/cdg278

Role of the CD47–SHPS-1 system in regulation of cell migration

Sei-ichiro Motegi1, Hideki Okazawa1, Hiroshi Ohnishi1, Ryuji Sato1, Yoriaki Kaneko2, Hisae Kobayashi1, Kyoko Tomizawa1, Tomokazu Ito1, Nakayuki Honma3, Hans-Jörg Bühring4, Osamu Ishikawa5 and Takashi Matozaki1

  1. Biosignal Research Center, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan
  2. Third Department of Internal Medicine, Gunma University School of Medicine, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan
  3. Pharmaceutical Research Laboratories, Kirin Brewery Co. Ltd, Takasaki, Gunma 370-1295, Japan
  4. Department of Internal Medicine II, Division of Hematology and Oncology, University of Tübingen, Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany
  5. Department of Dermatology, Gunma University School of Medicine, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan

Correspondence to:

Takashi Matozaki, E-mail: matozaki@showa.gunma-u.ac.jp

Received 27 November 2003; Accepted 15 April 2003; Revised 14 April 2003

SHPS-1 is a transmembrane protein whose extracellular region interacts with CD47 and whose cytoplasmic region undergoes tyrosine phosphorylation and there by binds the protein tyrosine phosphatase SHP-2. Formation of this complex is implicated in regulation of cell migration by an unknown mechanism. A CD47-Fc fusion protein or antibodies to SHPS-1 inhibited migration of human melanoma cells or of CHO cells overexpressing SHPS-1. Overexpression of wild-type SHPS-1 promoted CHO cell migration, whereas expression of the SHPS-1-4F mutant, which lacks the phosphorylation sites required for SHP-2 binding, had no effect. Antibodies to SHPS-1 failed to inhibit migration of CHO cells expressing SHPS-1-4F. SHPS-1 ligands induced the dephosphorylation of SHPS-1 and dissociation of SHP-2. Antibodies to SHPS-1 also enhanced Rho activity and induced both formation of stress fibers and adoption of a less polarized morphology in melanoma cells. Our results suggest that engagement of SHPS-1 by CD47 prevents the positive regulation of cell migration by this protein. The CD47–SHPS-1 system and SHP-2 might thus contribute to the inhibition of cell migration by cell–cell contact.

  • Keywords:

    • CD47,
    • cell migration,
    • cytoskeletal reorganization,
    • SHP-2,
    • SHPS-1